Classical conditioning is arguably the most fundamental tool we possess for adapting our behavior to a changing environment. Appetitive classical conditioning can be thought of as the process that establishes a learned association between reinforcement and the stimuli in the environment that signal its availability. This form of "reinforcement learning" provides organisms with a potent means to use predictive information to mold and guide preparatory action in an effort to maximize reward. The past three decades have been marked by major advances in our understanding of the neurobiological mechanisms that underlie reinforcement learning. In particular, short "phasic" bursts of neuronal activity in dopamine neurons, which are thought to produce rapid and transient increases in extracellular dopamine concentration throughout the striatum, have received considerable attention as a necessary component of the reinforcement process for both natural and drug reward. The central dogma in catecholamine research has held that dopamine transmission proceeds as a uniform broadcast signal from the midbrain to all target structures in the forebrain. However, there is mounting evidence that separate nuclei within the striatum may receive differential signals in response to primary rewards and conditioned cues at different stages in the learning process. It is hypothesized that this regional specificity in the dynamics and stability of dopamine signaling corresponds to the largely segregated roles in both learning and behavioral control that dopamine may play in these structures. The current proposal will test these hypotheses with three specific aims. Aim 1 will examine the impact of learning history and specific features of the task on the stability of phasic dopamine in the ventral striatum. Aim 2 will examine the influence of phasic dopamine on the activation of the striatum during different stages of learning and assess the coincident regional control of behavior. Aim 3 will examine phasic dopamine release in the ventral and dorsal striatum during multiple stages of reinforcement learning (acquisition, extended training and extinction) with the goal of correlating and comparing the development of specific behaviors to the profile of phasic signaling in each structure. PUBLIC HEALTH RELEVANCE: Although adaptive under normal circumstances, reinforcement learning is one of several contributing factors to the powerful control drug-related stimuli have over drug-seeking and drug-taking behaviors in many models of addiction. The phasic activation of the neuromodulator dopamine is implicated in both reinforcement learning and many aspects of drug abuse. The primary goal of this proposal is to examine the contribution of phasic dopamine release in specific brain regions to reinforcement and behavioral control.